The mortality rate from severe traumatic brain injury (TBI) in the United States alone amounts to 9-30 deaths per 100,000. Those suffering brain injury requiring medical treatment number 160-300 per 100,000, with approximately 20 percent of patients admitted to treatment facilities sustain a moderate to severe degree of injury as measured by the Glasgow Coma Score (GCS) of 3-12. Direct costs of brain injury, including the costs of treatment and long-term care, as well as indirect costs including disablement and the loss of productivity of brain injury patients and other such costs, are staggering.
Profound hypothermia has long been recognized as an effective means of cerebral protection from global ischemia. Clinical application of surface cooling to profound levels without extracorporeal bypass has been limited, however, because of the occurrence of ventricular fibrillation at temperatures below 27.degree. C. From 1974-1980, researchers reported successful total circulatory arrest using extracorporeal bypass at 10.degree. to 20.degree. C. for up to 50 minutes for repair of cardiac anomalies in children less than one year of age. Later, total circulatory arrest at temperatures of 8.degree.-10.degree. C. was also used in repair of adults' ascending aortic arch aneurysms.
These techniques of protection from global ischemia are in use today. However, the problem of intracranial hemorrhage during rewarming, together with the necessity of large vessel cannulation, has limited the application of hypothermia to surgical techniques.
Moderate hypothermia, in the range of 30.degree.-33.degree. C., is known to diminish brain tissue loss in laboratory animals when hypothermia is administered during and after ischemia. Improved behavioral outcome and reduced mortality have also been observed in such animals with moderate systemic hypothermia administered after injury. Moderate hypothermia has also been found to diminish excessive toxic neurotransmitter release and to prevent disruption of the blood-brain barrier in the test subjects of fluid percussion brain injury.
The potential clinical utility of moderate systemic hypothermia in treatment of patients with severe brain injury was investigated as early as 1958. There are reports of over 120 patients with severe brain injury producing coma who were treated with systemic cooling. All that can be concluded from this clinical literature is that toxicity is probably low at temperatures 30.degree. C. or greater and durations of less than 72 hours. The likely sources of toxicity from systemic cooling are coagulopathy, pulmonary complications, and cardiac ventricular arrhythmias.
Induced localized hypothermia has been used widely in the non- or pre-hospital treatment of numerous physiologic conditions. Cold packs of some sort are standard equipment in first aid kits, and are used to decrease peripheral blood flow (and commensurate swelling) in the event of contusion, insect bites or stings, nosebleeds, sprains, etc. Cold compresses to the head, of course, have long been a standard symptom-relieving measure for headaches and fever.
Brader, U.S. Pat. No. 4,750,493 disclosed a method of preventing brain damage during cardiac arrest, CPR, or severe shock. The method taught by Brader included cooling the extracranial area including the face during emergency care of cardiac arrest or severe shock. This spatially limited cooling method was suggested to promote maximum perfusion to the brain while lowering the oxygen demand of brain cells. However, this method did not encompass cooling of the entire body but of the head alone. Limitations of this technique are related to attempting to cool the head locally while warm blood circulates through the brain. In other words, Brader does not suggest or even relate to total systemic hypothermia. Further, Brader failed to appreciate the special difficulties involved in the treatment of severe brain trauma and required a hood- or cap-like topical cold pack to implement his method. Also nothing in Brader identifies the protocol for the introduction of medication to control toxicity or the rate at which a patient is to be returned to normal body temperature following the treatment, referred to herein as "rewarming".
Aside from topical and spatially limited cold applications, conventional hypothermia (body temperature less than 30.degree. C.) has been known to reduce brain metabolic requirements, which may lessen cerebral edema and neuropathological damage. Therefore, conventional hypothermia has been used in combination with barbiturate therapy to treat brain swelling and intracranial hypertension.
However, the aggressive use of conventional hypothermia has been abandoned during the past decade because (1) it was difficult to keep the body's core temperature at 30.degree. C. for several days; (2) clinical outcome was never shown to be improved by the technique; (3) cardiovascular instability often occurred during conventional hypothermia; and (4) the specific parameters of the depth of hypothermia, the duration of the hypothermia, and the method of rewarming were never established. Nor was the depth or duration of hypothermia specified by Brader.
Several recent experimental studies have suggested a protective effect of mild hypothermia on the brain during anoxia, hypoxia, and following head injury. It is known that a decrease in body temperature of 1.degree. C. to 3.degree. C. can minimize or prevent brain energy failure during hypoxia. Similar observations have led some clinicians to employ mild hypothermia in the treatment of brain swelling and intracranial hypertension. However, these observations have failed to identify a specific protocol to significantly improve the long term prognosis of head injury patients. Further, the use of hypothermia alone, without the identification of such a specific protocol, particularly in combination with the application of medications, has yet to address the problem of toxicity from systemic cooling in the patient.
The prior art has also failed to adequately address problems associated with so-called "rewarming shock." Rewarming shock has been shown to create troublesome complications of hypovolemic shock and abrupt intra-cranial pressure elevation when a patient's core temperature is returned to normal body temperature from an extended period of hypothermia. It is generally believed that vasodilation can often lead to a low arterial pressure during this rewarming phase.
Thus, there remains a need for a controllable and easily administered method of treating the victims' of severe brain trauma to achieve the perceived benefits of hypothermia. Such a method should preferably include the administration of medications to control both the effects of the brain injury and to balance the potential deleterious effects to the body of being subjected to reduced temperatures for an extended period. Effective hypothermia treatment should also control the desired depth of hypothermia, the optimal duration of hypothermia, and the rate and period of rewarming the patient and clearly identify when the administration of medications should be terminated.